Dosing & Uses
Dosage Forms & Strengths
capsule
- 40mg
Non-small Cell Lung Cancer
Indicated for locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC)
160 mg PO qDay for 14 days, then increase to 160 mg PO BID
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dose reductions for adverse reactions
-
Current dose is 160 mg PO qDay
- First dose reduction: 120 mg PO qDay
- Second dose reduction: 80 mg PO qDay
-
Current dose is 160 mg PO BID
- First dose reduction: 120 mg PO BID
- Second dose reduction: 80 mg PO BID
Central nervous system effects
- Intolerable Grade 2: Withhold until Grade ≤1 or baseline; resume at same or reduced dose, as clinically appropriate
- Grade 3: Withhold until Grade ≤1; resume at reduced dose
- Grade 4: Permanently discontinue
Interstitial lung disease (ILD)
- Suspected ILD: Withhold
- Confirmed ILD: Permanently discontinue
Hepatotoxicity
- ALT or AST >3x ULN with concurrent total bilirubin >1.5x ULN (without cholestasis or hemolysis): Permanently discontinue
-
Grade 3
- Withhold until Grade ≤1 or baseline
- Resume at same dose if resolves within 4 weeks
- Recurrent Grade 3 that resolves within 4 weeks: Resume at a reduced dose
-
Grade 4
- Withhold until Grade ≤1 or baseline
- Resume at reduced dose
- Reaction does not resolve within 4 weeks OR recurrent Grade 4: Permanently discontinue
Creatine phosphokinase (CPK) elevation
-
Withhold until resolves to baseline or ≤2.5x ULN, then
- CPK elevation >5x ULN: Resume at same dose
- CPK elevation >10x ULN or second occurrence of CPK elevation >5x ULN: Resume at reduced dose
Hyperuricemia
- Grade 3 or 4: Withhold until signs and symptoms improve, then resume at same or reduced dose
Other significant adverse reactions
- Intolerable Grade 2, Grade 3 or 4: Withhold until Grade ≤1 or baseline
- Resolves within 4 weeks: Resume at same or reduced dose
- Does not resolve within 4 weeks: Permanently discontinue
Renal impairment
- Mild-to-moderate (eGFR 30-90 mL/min): No dosage adjustment necessary
- Severe (eGFR <30 mL/min) or patients on dialysis: Pharmacokinetics are unknown
Hepatic impairment
- Mild (total bilirubin >1-1.5x ULN or AST >ULN): No dosage adjustment necessary
- Moderate or severe (total bilirubin >1.5x with any AST): Dosage not established
Dosing Considerations
Before initiating
- Discontinue strong or moderate CYP3A4 inhibitors for 3-5 half-lives of CYP3A4 inhibitor
- Evaluate liver function tests and uric acid levels
- Verify pregnancy status of females of childbearing potential before initiating
Patient selection
- Select patient based on presence of ROS1 rearrangement(s) in tumor specimens
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (172)
- adagrasib
adagrasib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- alfentanil
repotrectinib will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- amiodarone
amiodarone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
amiodarone will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - amobarbital
amobarbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- aprepitant
aprepitant will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- armodafinil
armodafinil will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- atazanavir
atazanavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- atorvastatin
atorvastatin will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- azithromycin
azithromycin will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- belzutifan
belzutifan will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bexarotene
bexarotene will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bicalutamide
bicalutamide will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- bosentan
bosentan will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butalbital
butalbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- capivasertib
repotrectinib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- carbamazepine
carbamazepine will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - carvedilol
carvedilol will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- cenobamate
cenobamate will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- chloramphenicol
chloramphenicol will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- clarithromycin
clarithromycin will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
clarithromycin will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - clonidine
repotrectinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- cobicistat
cobicistat will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- colchicine
repotrectinib will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- conivaptan
conivaptan will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- crizotinib
crizotinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- cyclosporine
cyclosporine will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
cyclosporine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - dabrafenib
dabrafenib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- daclatasvir
daclatasvir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- darunavir
darunavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
darunavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - dienogest/estradiol valerate
repotrectinib will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- dihydroergotamine
repotrectinib will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- diltiazem
diltiazem will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- disopyramide
repotrectinib will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- divalproex sodium
repotrectinib will decrease the level or effect of divalproex sodium by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- doxycycline
doxycycline will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- dronedarone
dronedarone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
dronedarone will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - drospirenone
repotrectinib will decrease the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- duvelisib
duvelisib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- elacestrant
elacestrant will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- elagolix
elagolix will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
elagolix will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - elexacaftor
elexacaftor will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- eliglustat
eliglustat will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- encorafenib
encorafenib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- entacapone
entacapone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- enzalutamide
enzalutamide will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erdafitinib
erdafitinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- erythromycin base
erythromycin base will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
erythromycin base will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
erythromycin ethylsuccinate will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
erythromycin lactobionate will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - erythromycin stearate
erythromycin stearate will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
erythromycin stearate will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of repotrectinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.
- ethinylestradiol
repotrectinib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- ethosuximide
repotrectinib will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- etrasimod
etrasimod, repotrectinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.
- etravirine
etravirine will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
etravirine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - everolimus
repotrectinib will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- fedratinib
fedratinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- fentanyl
repotrectinib will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- fexinidazole
fexinidazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- flibanserin
flibanserin will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- fluconazole
fluconazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- fluvoxamine
fluvoxamine will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- fosamprenavir
fosamprenavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- fosaprepitant
fosaprepitant will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- fosphenytoin
fosphenytoin will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of fosphenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - fostamatinib
fostamatinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
fostamatinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- grapefruit
grapefruit will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
grapefruit will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - haloperidol
haloperidol will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- ibrexafungerp
ibrexafungerp will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- ibrutinib
ibrutinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- iloperidone
iloperidone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- imatinib
imatinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- indinavir
indinavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- isavuconazonium sulfate
isavuconazonium sulfate will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
isavuconazonium sulfate will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - isoniazid
isoniazid will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- istradefylline
istradefylline will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- itraconazole
itraconazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
itraconazole will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - ivacaftor
ivacaftor will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
ivacaftor will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - ivosidenib
ivosidenib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ketoconazole
ketoconazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
ketoconazole will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - lapatinib
lapatinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
lapatinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - larotrectinib
larotrectinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- lasmiditan
lasmiditan will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- ledipasvir/sofosbuvir
ledipasvir/sofosbuvir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- lefamulin
lefamulin will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- lenacapavir
lenacapavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- letermovir
letermovir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- levoketoconazole
levoketoconazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- levonorgestrel oral
repotrectinib will decrease the level or effect of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
repotrectinib will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- lomitapide
lomitapide will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- lonafarnib
lonafarnib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
lonafarnib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - lopinavir
lopinavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
lopinavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - lorlatinib
lorlatinib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mavacamten
mavacamten will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mefloquine
mefloquine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- metronidazole
metronidazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- midazolam
repotrectinib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- mifepristone
mifepristone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- mitapivat
mitapivat will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
mitapivat will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - mitotane
mitotane will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mobocertinib
mobocertinib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- modafinil
modafinil will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nefazodone
nefazodone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
nefazodone will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - nelfinavir
nelfinavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
nelfinavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - neratinib
neratinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
nirmatrelvir/ritonavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - nirogacestat
repotrectinib will decrease the level or effect of nirogacestat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- norgestrel
repotrectinib will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure to an extent that could reduce effectiveness of hormonal contraceptives. Advise females to use an effective nonhormonal contraceptive.
- olutasidenib
olutasidenib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- osimertinib
osimertinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- pacritinib
repotrectinib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- pentobarbital
pentobarbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pexidartinib
pexidartinib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of phenobarbital by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - phenytoin
phenytoin will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - pimozide
repotrectinib will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- ponatinib
ponatinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- posaconazole
posaconazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
posaconazole will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - primidone
primidone will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of primidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - propafenone
propafenone will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- quinidine
quinidine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - quinine
quinine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- ranolazine
ranolazine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- repaglinide
repotrectinib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- reserpine
reserpine will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- ribociclib
ribociclib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- rifabutin
rifabutin will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ritlecitinib
ritlecitinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- ritonavir
ritonavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
ritonavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - rolapitant
rolapitant will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- rucaparib
rucaparib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- saquinavir
saquinavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
saquinavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - schisandra
schisandra will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- secobarbital
secobarbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- selumetinib
selumetinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- sertraline
sertraline will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- sirolimus
repotrectinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- sotorasib
sotorasib will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sparsentan
sparsentan will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- St John's Wort
St John's Wort will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- stiripentol
stiripentol, repotrectinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Stiripentol inhibits and induces CYP3A4.
stiripentol will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - suvorexant
suvorexant will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- tacrolimus
tacrolimus will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
repotrectinib will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information. - telotristat ethyl
telotristat ethyl will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tetracycline
tetracycline will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- tezacaftor
tezacaftor will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- theophylline
repotrectinib will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- thioridazine
repotrectinib will decrease the level or effect of thioridazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- ticagrelor
ticagrelor will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- tipranavir
tipranavir will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- triazolam
repotrectinib will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- tucatinib
tucatinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
tucatinib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - valproic acid
repotrectinib will decrease the level or effect of valproic acid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repotrectinib is a CYP3A4 inducer. Avoid coadministration with CYP3A substrates where minimal concentration changes can cause reduced efficacy, unless otherwise recommended their prescribing information.
- vandetanib
vandetanib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- vemurafenib
vemurafenib will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- venetoclax
venetoclax will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- verapamil
verapamil will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
verapamil will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - voriconazole
voriconazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- voxelotor
voxelotor will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
All grades
- Decreased hemoglobin (73%)
- Dizziness (63%)
- Increased creatine phosphokinase (CPK) (57%)
- Increased gamma-glutamyl transferase (GGT) (48%)
- Dysgeusia (48%)
- Peripheral neuropathy (47%)
- Decreased lymphocytes (43%)
- Increased aspartate aminotransferase (AST) (40%)
- Constipation (36%)
- Decreased leukocytes (36%)
- Decreased neutrophils (34%)
- Increased alanine transaminase (ALT) (34%)
- Dyspnea (30%)
- Increased sodium (29%)
- Ataxia (28%)
- Increased alkaline phosphatase (26%)
- Increased activated partial thromboplastin (aPTT) (25%)
- Fatigue (24%)
- Cognitive disorders (23%)
- Increased glucose (23%)
- Muscular weakness (21%)
- Increased urate (21%)
- Decreased glucose (21%)
- Increased INR (20%)
- Headache (19%)
- Nausea (19%)
- Cough (14%)
- Increased weight (14%)
- Diarrhea (13%)
- Edema (12%)
- Myalgia (12%)
- Vision disorders (11%)
Grade 3 or 4
- Increased GGT (12%)
- Increased urate (11%)
1-10%
All grades
- Vomiting (10%)
Grade 3 or 4
- Decreased lymphocytes (10%)
- Decreased neutrophils (8%)
- Dyspnea (7%)
- Increased CPK (6%)
- Decreased hemoglobin (5%)
- Decreased leukocytes (4.7%)
- Increased ALT (3.1%)
- Increased alkaline phosphatase (2.3%)
- Dizziness (1.9%)
- Peripheral neuropathy (1.9%)
- Increased weight (1.9%)
- Increased AST (1.9%)
- Muscular weakness (1.5%)
- Increased glucose (1.5%)
- Fatigue (1.1%)
<1%
Grade 3 or 4
- Cognitive disorders (0.8%)
- Vomiting (0.8%)
- Edema (0.8%)
- Ataxia (0.4%)
- Decreased glucose (0.4%)
- Nausea (0.4%)
- Diarrhea (0.4%)
- Myalgia (0.4%)
- Increased sodium (0.4%)
- Increased aPTT (0.4%)
Warnings
Contraindications
None
Cautions
Hyperuricemia may occur; monitor serum uric acid levels before initiating and periodically during treatment; initiate urate-lowering medications as clinically indicated
Associated with skeletal fractures; promptly evaluate signs or symptoms (eg, pain, changes in mobility, deformity) of fractures; no data are available on effects of repotrectinib on healing of known fractures and risk of future fractures
Based studies and its mechanism of action, fetal harm may occur when administer to pregnant females
Myalgia
- May cause myalgia with or without creatine phosphokinase (CPK) elevation
- Monitor serum CPK levels every 2 weeks during first month of treatment and as needed if unexplained muscle pain, tenderness, or weakness reported
- Initiate supportive care as clinically indicated
Hepatoxicity
- Hepatoxicity reported
- Monitor liver function tests every 2 weeks during first month of treatment, then monthly thereafter and as clinically indicated
- Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue based on severity
Interstitial lung disease (ILD)/pneumonitis
- May cause ILD/pneumonitis
- Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis
- Immediately withhold if ILD/pneumonitis is suspected
- If confirmed, permanently discontinue
Central nervous system (CNS) adverse reactions
CNS adverse reactions (eg, dizziness, ataxia, cognitive disorders) may occur
Sleep (eg, insomnia, hypersomnia) and mood disorders also occurred
Reported incidences were similar in patients with or without CNS metastases
Advise patients and caregivers of CNS adverse reactions
Advise patients not to drive or use machines if CNS adverse reactions occur
Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue based on severity
Drug interaction overview
Strong and moderate CYP3A inhibitors
- Avoid coadministration
- Discontinue CYP3A inhibitors for 3-5 elimination half-lives of CYP3A4 inhibitor before initiating
- Strong or moderate CYP3A inhibitors may increase repotrectinib exposure and risk of toxicities
P-gp inhibitors
- Avoid coadministration
- P-gp inhibitors may increase repotrectinib exposure and severity of adverse reactions
Strong and moderate CYP3A inducers
- Avoid coadministration
- Strong or moderate CYP3A inducers may decrease repotrectinib plasma concentrations and its efficacy
Sensitive CYP3A substrates
- Avoid coadministration with CYP3A substrates, where minimal concentration changes can cause reduced efficacy
- If unavoidable, increase CYP3A4 substrate dosage in accordance with approved product labeling
Hormonal contraceptives
- Avoid coadministration
- Advise females to use an effective nonhormonal contraceptives
- Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure and may reduce effectiveness of hormonal contraceptives
Pregnancy & Lactation
Pregnancy
Based studies and its mechanism of action, fetal harm may occur when administered to pregnant females
There are no available data on use in pregnant females
Verify pregnancy status of females of childbearing potential before initiating
Contraception
- Females of childbearing potential: Use effective non-hormonal contraception during treatment and for 2 months following last dose
- Repotrectinib render some hormonal contraceptives ineffective
- Male patients with female partners of childbearing potential: Use effective contraception during treatment and for 4 months following last dose
Animal data
- Oral administration of repotrectinib to pregnant rats during organogenesis resulted in fetal malformations at doses approximately 0.3x the recommended dose of 160 mg BID based on BSA
Lactation
There are no data on drug presence in human milk or its effects on either breastfed children or on milk production
Advise lactating women to discontinue breastfeeding during treatment and for 10 days after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC
Fusion proteins that include ROS1 domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation
Absorption
Steady-state peak plasma concentration: 713 ng/mL
Peak plasma time: 2-3 hr (post single 40-mg to 240-mg dose)
AUC (steady-state): 7,210 ng⋅hr/mL
Steady-state achieved within 14 days
Absolute bioavailability: 45.7%
Distribution
Vd: 432 L (single 160-mg dose)
Protein bound: 95.4%
Blood-to-plasma ratio: 0.56
Metabolism
Primarily metabolized by CYP3A4 followed by secondary glucuronidation
Elimination
Clearance: 15.9 L/hr (single 160-mg oral dose)
Half-life: 50.6 hr (single dose); 35.4 hr (steady-state)
Excretion (single dose)
- Urine: 4.84% (0.56% unchanged)
- Feces: 88.8% (50.6% unchanged)
Administration
Oral Administration
Take orally at approximately same time each day with or without food
Swallow capsules whole; do NOT open, chew, crush, or dissolve
Do not take if broken, cracked, or damaged
If dose missed or vomited, skip dose and resume at its regularly schedule time
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
Formulary
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